tbuckley/cabot-search huggingface dataset:
Cross-talk between Myeloid and B Cells Shapes the Distinct Microenvironments of Primary and Secondary Liver Cancer
Authors: Zhihang Chen, Guopei Zhang, Xiaoxue Ren, Zhijia Yao, Qian Zhou, Xuxin Ren, Shuling Chen, Lixia Xu, Kaiyu Sun, Qianwen Zeng, Ming Kuang, Dong-Ming Kuang, Sui Peng
Journal: Cancer Research (2023)

The tumor microenvironment is distinctive in primary and secondary liver cancer. B cells represent an important component of immune infiltrates. Here, we demonstrated that B cells are an important regulator in hepatocellular carcinoma (HCC) and colorectal cancer liver metastasis (CRLM) microenvironments. B cells displayed distinct developmental trajectories in HCC and CRLM. Single-cell analysis revealed that IgG+ plasma cells preferentially accumulated in HCC, whereas IgA+ plasma cells were preferentially enriched in CRLM. Mechanistically, IgG+ plasma cells in HCC were recruited by tumor-associated macrophages via the CXCR3-CXCL10 axis, whereas IgA+ plasma cells in CRLM were recruited by metastatic tumor cells via CCR10-CCL28 signaling. Functionally, IgG+ plasma cells preferentially promoted protumorigenic macrophages formation in HCC, and IgA+ plasma cells preferentially induced granulocytic myeloid-derived suppressor cells activation in CRLM. Clinically, increased infiltration of IgG+ plasma cells and macrophages in HCC was correlated to worse survival, whereas increased intratumoral IgA+ plasma cells and neutrophils in CRLM indicated poor prognosis. Taken together, this study demonstrated plasma and myeloid cell-mediated immunosuppression in HCC and CRLM, suggesting that selectively modulating primary or secondary tumor-related immunosuppressive regulatory networks might reprogram the microenvironment and provide an immunotherapeutic strategy for treating liver cancer.The immunomodulatory patterns of tumor-infiltrating B cells are distinct in primary and secondary liver cancer, with plasma cells mediating important physiologic processes that drive cancer progression.
A new procedure for elimination of atrial fibrillation associated with mitral valve disease: a proof-of-concept study
Authors: Liangwan Chen, Qianzhen Li, Junyi Chen, Zhihuang Qiu, Jun Xiao, Mirong Tang, Qingsong Wu, Yue Shen, Xiaofu Dai, Guanhua Fang, Heng Lu
Journal: International Journal of Surgery (2023)

Left atrial enlargement and fibrosis have been linked to the pathogenesis of atrial fibrillation (AF). The authors aimed to introduce a novel concept and develop a new procedure for AF treatment based on these characteristics.The study included three stages. The first stage was a descriptive study to clarify the characteristics of the left atrial enlargement and fibrosis' distribution in patients with mitral valve disease and long-standing persistent AF. Based on these characteristics, the authors introduced a novel concept for AF treatment, and then translated it into a new procedure. The second stage was a proof-of-concept study with this new procedure. The third stage was a comparative effectiveness research to compare the clinical outcomes between patients with this new procedure and those who received Cox-Maze IV treatment.Based on the nonuniform fashion of left atrial enlargement and fibrosis' distribution, the authors introduced a novel concept: reconstructing a left atrium with appropriate geometry and uniform fibrosis' distribution for proper cardiac conduction, and translated it into a new procedure: left atrial geometric volume reduction combined with left appendage base closure. As compared to the Cox-Maze IV procedure, the new procedure spent significantly shorter total surgery time, cardiopulmonary bypass time, and aortic cross-clamp time ( P <0.001). Besides, the new procedure was related to a shorter ICU stay period (odd ratio (OR)=0.45, 95% CI=0.26-0.78), lower costs (OR=0.15, 95% CI=0.08-0.29), and a higher rate of A wave of transmitral and transtricuspid flow reappearance (OR=1.76, 95% CI=1.02-3.04).The new procedure is safe and effective for eliminating AF associated with mitral valve disease.
Supraphysiological Androgens Promote the Tumor Suppressive Activity of the Androgen Receptor through cMYC Repression and Recruitment of the DREAM Complex
Authors: Michael D. Nyquist, Ilsa M. Coleman, Jared M. Lucas, Dapei Li, Brian Hanratty, Hannah Meade, Elahe A. Mostaghel, Stephen R. Plymate, Eva Corey, Michael C. Haffner, Peter S. Nelson
Journal: Cancer Research (2023)

The androgen receptor (AR) pathway regulates key cell survival programs in prostate epithelium. The AR represents a near-universal driver and therapeutic vulnerability in metastatic prostate cancer, and targeting AR has a remarkable therapeutic index. Though most approaches directed toward AR focus on inhibiting AR signaling, laboratory and now clinical data have shown that high dose, supraphysiological androgen treatment (SPA) results in growth repression and improved outcomes in subsets of patients with prostate cancer. A better understanding of the mechanisms contributing to SPA response and resistance could help guide patient selection and combination therapies to improve efficacy. To characterize SPA signaling, we integrated metrics of gene expression changes induced by SPA together with cistrome data and protein-interactomes. These analyses indicated that the dimerization partner, RB-like, E2F, and multivulval class B (DREAM) complex mediates growth repression and downregulation of E2F targets in response to SPA. Notably, prostate cancers with complete genomic loss of RB1 responded to SPA treatment, whereas loss of DREAM complex components such as RBL1/2 promoted resistance. Overexpression of MYC resulted in complete resistance to SPA and attenuated the SPA/AR-mediated repression of E2F target genes. These findings support a model of SPA-mediated growth repression that relies on the negative regulation of MYC by AR leading to repression of E2F1 signaling via the DREAM complex. The integrity of MYC signaling and DREAM complex assembly may consequently serve as determinants of SPA responses and as pathways mediating SPA resistance.
Prediction of early functional outcomes in patients after robotic-assisted total knee arthroplasty: a nomogram prediction model
Authors: Xudong Duan, Yiwei Zhao, Jiewen Zhang, Ning Kong, Ruomu Cao, Huanshuai Guan, Yiyang Li, Kunzheng Wang, Pei Yang, Run Tian
Journal: International Journal of Surgery (2023)

Robotic-assisted total knee arthroplasty (RA-TKA) is becoming more and more popular as a treatment option for advanced knee diseases due to its potential to reduce operator-induced errors. However, the development of accurate prediction models for postoperative outcomes is challenging. This study aimed to develop a nomogram model to predict the likelihood of achieving a beneficial functional outcome. The beneficial outcome is defined as a postoperative improvement of the functional Knee Society Score (fKSS) of more than 10 points, 3 months after RA-TKA by early collection and analysis of possible predictors.This is a retrospective study on 171 patients who underwent unilateral RA-TKA at our hospital. The collected data included demographic information, preoperative imaging data, surgical data, and preoperative and postoperative scale scores. Participants were randomly divided into a training set ( N =120) and a test set ( N =51). Univariate and multivariate logistic regression analyses were employed to screen for relevant factors. Variance inflation factor was used to investigate for variable collinearity. The accuracy and stability of the models were evaluated using calibration curves with the Hosmer-Lemeshow goodness-of-fit test, consistency index and receiver operating characteristic curves.Predictors of the nomogram included preoperative hip-knee-ankle angle deviation, preoperative 10-cm Visual Analogue Scale score, preoperative fKSS score and preoperative range of motion. Collinearity analysis with demonstrated no collinearity among the variables. The consistency index values for the training and test sets were 0.908 and 0.902, respectively. Finally, the area under the receiver operating characteristic curve was 0.908 (95% CI 0.846-0.971) in the training set and 0.902 (95% CI 0.806-0.998) in the test set.A nomogram model was designed hereby aiming to predict the functional outcome 3 months after RA-TKA in patients. Rigorous validation showed that the model is robust and reliable. The identified key predictors include preoperative hip-knee-ankle angle deviation, preoperative visual analogue scale score, preoperative fKSS score, and preoperative range of motion. These findings have major implications for improving therapeutic interventions and informing clinical decision-making in patients undergoing RA-TKA.
Development and application of nanomaterials, nanotechnology and nanomedicine for treating hematological malignancies
Authors: Jinxin Li, Qiwei Wang, Yingli Han, Lingli Jiang, Siqi Lu, Beini Wang, Wenchang Qian, Meng Zhu, He Huang, Pengxu Qian
Journal: Journal of Hematology & Oncology (2023)

Abstract Hematologic malignancies (HMs) pose a serious threat to patients’ health and life, and the five-year overall survival of HMs remains low. The lack of understanding of the pathogenesis and the complex clinical symptoms brings immense challenges to the diagnosis and treatment of HMs. Traditional therapeutic strategies for HMs include radiotherapy, chemotherapy, targeted therapy and hematopoietic stem cell transplantation. Although immunotherapy and cell therapy have made considerable progress in the last decade, nearly half of patients still relapse or suffer from drug resistance. Recently, studies have emerged that nanomaterials, nanotechnology and nanomedicine show great promise in cancer therapy by enhancing drug targeting, reducing toxicity and side effects and boosting the immune response to promote durable immunological memory. In this review, we summarized the strategies of recently developed nanomaterials, nanotechnology and nanomedicines against HMs and then proposed emerging strategies for the future designment of nanomedicines to treat HMs based on urgent clinical needs and technological progress.
Neoadjuvant intensity modulated radiotherapy for a single and small (≤5 cm) hepatitis B virus-related hepatocellular carcinoma predicted to have high risks of microvascular invasion: a randomized clinical trial
Authors: Xubiao Wei, Yabo Jiang, Shuang Feng, Chongde Lu, Lei Huo, Bin Zhou, Yan Meng, Wan Yee Lau, Yaxin Zheng, Shuqun Cheng
Journal: International Journal of Surgery (2023)

The presence of microvascular invasion (MVI) significantly impairs postoperative long-term survival of patients with hepatocellular carcinoma (HCC). The role of neoadjuvant radiotherapy (RT) in treating patients with an early-stage HCC predicted to have high risks of MVI remains to be explored.Consecutive patients with a resectable single and small (≤5 cm) hepatitis B virus-related HCC predicted to have high risks of MVI were randomized 1:1 to receive either neoadjuvant intensity modulated radiation therapy (18 Gy with fractionated doses of 3 Gy) followed by surgery 4 weeks later or upfront surgery. The primary endpoint was disease-free survival (DFS). The secondary outcomes included overall survival (OS), objective response rate, RT-related toxicity and surgical complications.There were 30 patients randomized to each of the two groups. In the neoadjuvant RT group, three patients violated the study protocol, with two having upfront hepatectomy and one radiofrequency ablation after RT. The objective response rate after RT was 25.0% (7/28), but 2 patients suffered from grade 3 liver toxicity. The median follow-up was 68 months (interquartile range, 58-70 months) in the neoadjuvant RT group, and 68 months (interquartile range, 62-75 months) in the upfront surgery group. On intention-to-treat analysis, the median DFS and median OS were not reached in both the 2 arms. The 1-year, 2-year, 3-year and 5-year DFS rates for the neoadjuvant RT group were 86.7%, 76.7%, 60.0% and 56.3%, versus 90.0%, 66.7%, 52.8% and 45.7% in the upfront surgery group ( P =0.448), respectively. The corresponding OS rates were 96.7%, 86.7%, 83.3% and 72.7%, versus 100.0%, 93.3%, 79.6% and 60.7% ( P = 0.399).For patients with a resectable single and small hepatitis B virus-related HCC predicted to have high risks of MVI, neoadjuvant RT gave a promising response rate with a mild toxicity. Nevertheless, the neoadjuvant RT yielded similar long-term DFS and OS rates compared with patients who underwent upfront surgery.
Comment on ‘Duloxetine for rehabilitation after total knee arthroplasty: a systematic review and meta-analysis’
Authors: Meiru Chen, Dandan Zhang, Wenhui Hu, Xiumei Tang, Xiaoling Hou
Journal: International Journal of Surgery (2023)

aDepartment of Orthopedics, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, 610041, Chengdu, P.R. China, Trauma center, West China Hospital, Sichuan University, 610041, Chengdu, P.R. China bDepartment of Respiratory and Critical Care Medicine, Med-X Center for Manufacturing, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, 610041, P.R. China cHealth Management Center, General Practice Medical Center, West China Hospital, Sichuan University/Institute of Hospital Management, West China Hospital, Sichuan University, Chengdu, 610041, P.R. China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article Published online ■ ■ *Corresponding author. Address: Professor of nursing, Department of Orthopedics, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, 610041, Chengdu, P.R. China. Tel: +86 189 8060 1383. E-mail address: [email protected] (X. Hou). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/
Organ-on-chip: a new paradigm for clinical trials – correspondence
Authors: Hitesh Chopra, Sandip Chakraborty, Shopnil Akash, Chiranjib Chakraborty, Kuldeep Dhama
Journal: International Journal of Surgery (2023)

Chopra, Hitesh; Chakraborty, Sandip; Akash, Shopnil; Chakraborty, Chiranjib; Dhama, Kuldeep Author Information
Examining the differences between how doctors and artificial intelligence chatbots handle patient symptoms
Authors: Ruhul Amin, Ronald Darwin, Biplab Kumar Dey, Kuldeep Dhama, Talha Bin Emran
Journal: International Journal of Surgery (2023)

Amin, Ruhul PhD; Darwin, Ronald PhD; Dey, Biplab Kumar PhD; Dhama, Kuldeep PhD; Bin Emran, Talha PhD Author Information
Whole Slide Imaging-Based Prediction of <i>TP53</i> Mutations Identifies an Aggressive Disease Phenotype in Prostate Cancer
Authors: Marija Pizurica, Maarten Larmuseau, Kim Van der Eecken, Louise de Schaetzen van Brienen, Francisco Carrillo-Perez, Simon Isphording, Nicolaas Lumen, Jo Van Dorpe, Piet Ost, Sofie Verbeke, Olivier Gevaert, Kathleen Marchal
Journal: Cancer Research (2023)

Abstract In prostate cancer, there is an urgent need for objective prognostic biomarkers that identify the metastatic potential of a tumor at an early stage. While recent analyses indicated TP53 mutations as candidate biomarkers, molecular profiling in a clinical setting is complicated by tumor heterogeneity. Deep learning models that predict the spatial presence of TP53 mutations in whole slide images (WSI) offer the potential to mitigate this issue. To assess the potential of WSIs as proxies for spatially resolved profiling and as biomarkers for aggressive disease, we developed TiDo, a deep learning model that achieves state-of-the-art performance in predicting TP53 mutations from WSIs of primary prostate tumors. In an independent multifocal cohort, the model showed successful generalization at both the patient and lesion level. Analysis of model predictions revealed that false positive (FP) predictions could at least partially be explained by TP53 deletions, suggesting that some FP carry an alteration that leads to the same histological phenotype as TP53 mutations. Comparative expression and histologic cell type analyses identified a TP53-like cellular phenotype triggered by expression of pathways affecting stromal composition. Together, these findings indicate that WSI-based models might not be able to perfectly predict the spatial presence of individual TP53 mutations but they have the potential to elucidate the prognosis of a tumor by depicting a downstream phenotype associated with aggressive disease biomarkers. Significance: Deep learning models predicting TP53 mutations from whole slide images of prostate cancer capture histologic phenotypes associated with stromal composition, lymph node metastasis, and biochemical recurrence, indicating their potential as in silico prognostic biomarkers. See related commentary by Bordeleau, p. 2809
Proportion of early extubation and short-term outcomes after esophagectomy: a retrospective cohort study
Authors: Yuki Hirano, Takaaki Konishi, Hidehiro Kaneko, Hidetaka Itoh, Satoru Matsuda, Hirofumi Kawakubo, Kazuaki Uda, Hiroki Matsui, Kiyohide Fushimi, Hiroyuki Daiko, Osamu Itano, Hideo Yasunaga, Yuko Kitagawa
Journal: International Journal of Surgery (2023)

The proportion of early extubation after esophagectomy varies among hospitals; however, the impact on clinical outcomes is unclear. The aim of this retrospective study was to evaluate associations between the proportion of early extubation in hospitals and short-term outcomes after esophagectomy. Because there is no consensus regarding the optimal timing for extubation, the authors considered that hospitals' early extubation proportion reflects the hospital-level extubation strategy.Data of patients who underwent oncologic esophagectomy (July 2010-March 2019) were extracted from a Japanese nationwide inpatient database. The proportion of patients who underwent early extubation (extubation on the day of surgery) at each hospital was assessed and grouped by quartiles: very low- (<11%), low- (11-37%), medium- (38-83%), and high-proportion (≥84%) hospitals. The primary outcome was respiratory complications; secondary outcomes included reintubation, anastomotic leakage, other major complications, and hospitalization costs. Multivariable regression analyses were performed, adjusting for patient demographics, cancer treatments, and hospital characteristics. A restricted cubic spline analysis was also performed for the primary outcome.Among 37 983 eligible patients across 545 hospitals, early extubation was performed in 17 931 (47%) patients. Early extubation proportions ranged from 0-100% across hospitals. Respiratory complications occurred in 10 270 patients (27%). Multivariable regression analyses showed that high- and medium-proportion hospitals were significantly associated with decreased respiratory complications [odds ratio, 0.46 (95% CI, 0.36-0.58) and 0.43 (0.31-0.60), respectively], reintubation, and hospitalization costs when compared with very low-proportion hospitals. The risk of anastomotic leakage and other major complications did not differ among groups. The restricted cubic spline analysis demonstrated a significant inverse dose-dependent association between the early extubation proportion and the risk of respiratory complications.A higher proportion of early extubation in a hospital was associated with a lower occurrence of respiratory complications, highlighting a potential benefit of early extubation after esophagectomy.
Effect of laparoscopic sleeve gastrectomy on mobilization of site-specific body adipose depots: a prospective cohort study
Authors: Beibei Cui, Junhong Duan, Liyong Zhu, Guohui Wang, Xulong Sun, Zhihong Su, Yunjie Liao, Bo Yi, Pengzhou Li, Weizheng Li, Zhi Song, Zheng Li, Haibo Tang, Pengfei Rong, Shaihong Zhu
Journal: International Journal of Surgery (2023)

Effect of bariatric surgery on mobilization of site-specific body adipose depots is not well investigated. Herein, the authors conducted a prospective cohort study to assess whether bariatric surgery can differentially affect specific fat storage pools and to further investigate correlations between site-specific fat mobilization and clinical outcomes.In this single-centre prospective cohort study, 49 participants underwent laparoscopic sleeve gastrectomy (LSG) from 24 May 2022 to 20 October 2022 and underwent MRI to estimate subcutaneous fat area, visceral fat area (VFA), hepatic and pancreatic proton density fat fraction (PDFF) at baseline and 3 months after surgery. The protocol for this study was registered on clinicaltrials.gov.Among 49 patients who met all inclusion criteria, the median [interquartile range (IQR)] age was 31.0 (23.0-37.0) years, the median (IQR) BMI was 38.1 (33.7-42.2) kg/m 2 and 36.7% were male. Median (IQR) percentage hepatic PDFF loss was the greatest after bariatric surgery at 68.8% (47.3-79.7%), followed by percentage pancreatic PDFF loss at 51.2% (37.0-62.1%), percentage VFA loss at 36.0% (30.0-42.4%), and percentage subcutaneous fat area loss at 22.7% (17.2-32.4%) ( P <0.001). By calculating Pearson correlation coefficient and partial correlation coefficient, the positive correlations were confirmed between change in VFA and change in glycated haemoglobin ( r =0.394, P =0.028; partial r =0.428, P =0.042) and between change in hepatic PDFF and change in homoeostatic model assessment of insulin resistance ( r =0.385, P =0.025; partial r =0.403, P =0.046).LSG preferentially mobilized hepatic fat, followed by pancreatic fat and visceral adipose tissue, while subcutaneous adipose tissue was mobilized to the least extent. Reduction in visceral adipose tissue and hepatic fat is independently associated with the improvement of glucose metabolism after LSG.
The WHO has ended public health emergency of international concern for mpox: assessment of upside and downside of this decision
Authors: Rapty Sarker, A.S.M. Roknuzzaman, Mohammad Shahriar, Mohiuddin Ahmed Bhuiyan, Md. Rabiul Islam
Journal: International Journal of Surgery (2023)

Sarker, Rapty; Roknuzzaman, A.S.M.; Shahriar, Mohammad; Bhuiyan, Mohiuddin Ahmed; Islam, Md. Rabiul Author Information
VarID2 quantifies gene expression noise dynamics and unveils functional heterogeneity of ageing hematopoietic stem cells
Authors: Reyna Edith Rosales-Alvarez, Jasmin Rettkowski, Josip Stefan Herman, Gabrijela Dumbović, Nina Cabezas-Wallscheid, Dominic Grün
Journal: Genome biology (2023)

Abstract Variability of gene expression due to stochasticity of transcription or variation of extrinsic signals, termed biological noise, is a potential driving force of cellular differentiation. Utilizing single-cell RNA-sequencing, we develop VarID2 for the quantification of biological noise at single-cell resolution. VarID2 reveals enhanced nuclear versus cytoplasmic noise, and distinct regulatory modes stratified by correlation between noise, expression, and chromatin accessibility. Noise levels are minimal in murine hematopoietic stem cells (HSCs) and increase during differentiation and ageing. Differential noise identifies myeloid-biased Dlk1+ long-term HSCs in aged mice with enhanced quiescence and self-renewal capacity. VarID2 reveals noise dynamics invisible to conventional single-cell transcriptome analysis.